Acute pancreatitis is a disease of variable severity in which patients can experience mild or severe attacks. Most observers believe that acute pancreatitis results from an early intra-acinar cell activation of inactive zymogens into their active forms. Following this early activation, a trypsin cascade occurs in the gland which leads to the auto-digestion of acinar cells. Recent experimental data indicate that synthesis and release of pro-inflammatory cytokines and chemokines are also responsible for local injury and systemic dispersion of the inflammatory mediators. Experimental studies also provide evidence for the involvement of the immune system in the development of pancreatitis, including lymphocyte and neutrophil activation. However, the factors that will dictate the ultimate severity of the attack are still unknown. Following an attack, the pancreas completely recovers or becomes fibrotic through the action of newly described mediators within the pancreas such as TGF-beta and IGF-1 and the presence of pancreatic stellate cell that is known to play a crucial role in the fibrogenesis.